Diesel exhaust particles are highly respirable with mutagenic and carcinogenic compounds adsorbed on their surface. Inhalation of high levels of diesel exhaust in laboratory animals results in lung tumors. In 1989, the International Agency for Research on Cancer classified diesel exhaust as a probable human carcinogen. Evidence of the carcinogenicity of diesel exhaust in humans was mainly based on studies in U.S. railroad workers published by our research group. In the U.S., the railroad industry changed from steam to diesel power in the 1950's such that by 1959, 95% of the locomotives were diesel. In a case-control study of 1256 lung cancer deaths in railroad workers collected over one year (1981-1982), workers with 20 years of work in a diesel exhaust exposed job had an elevated odds ratio of 1.41 (95% CI = 1.06, 1.88) of dying of lung cancer, adjusting for cigarette smoking and asbestos exposure. Similar associations were found in a retrospective cohort study of 55,407 railroad workers age 40 through 64 in 1959 with 10 to 20 years of railroad service, with death ascertainment through 1980. Workers age 40-44 with work in a diesel exhaust exposed job in 1959 had an elevated relative risk of lung cancer 1.45 (95% CI = 1.11, 1.89). These workers, aged 40-44 in 1959, had the longest duration of future exposure to diesel. However, it has not been possible to conclude that diesel exhaust is a definite human carcinogen. A weakness of past epidemiologic studies has been lack of measures of diesel exposure and insufficient years of follow-up. This study proposes to complete vital-status follow-up of the cohort of 55,407 railroad workers for the years 1981 through 1996. It is anticipated that up to 24,000 additional deaths will be ascertained. These additional deaths will permit the evaluation of exposure-response relationship in a large cohort of workers with 25-35 years of exposure and over 35 years of follow-up. Exposure will be quantified by job category, years of exposure to diesel exhaust, and by cumulative estimated diesel exhaust exposure based on previously collected industrial hygiene measurements. This large cohort provides a unique opportunity to detect (or refute) suggested carcinogenic effects of diesel exhaust based on animal toxicology and limited epidemiologic studies.